1. Field of the Invention
The present invention relates to a system for the measurement of the efficacy of stored red blood cells using microvascular devices. More particularly, the present invention relates to microvascular devices that simulate the capillary networks and their physiological function and measurement devices that measure criteria of a sample of previously stored blood to determine the sample's efficacy prior to transfusion.
2. Description of Related Art
In the last few years, several clinical studies have seriously questioned the safety and efficacy of transfusing stored red blood cells (RBCs) in a range of clinical situations [Koch et al. 2008; Weinberg et al. 2008; Murphy et al. 2007, 2008; Zimrin and Hess 2009]. During refrigerated storage, RBCs lose ATP, membrane and volume, change shape, demonstrate a significant reduction of deformability, and, as a result, may become unfit for circulation [Hess and Greenwalt 2002; Zimrin and Hess 2009; Tinmouth and Chin-Yee 2001]. If transfused, these cells may diminish local delivery of oxygen by retarding the flow of blood through larger vessels and by plugging or bypassing the capillaries of microvascular networks, and thus ultimately cause ischemia of tissues and critical end organs [Murthy et al. 2007; Tsai et al. 2004]. So far, physicians have been unable to predict how well RBCs from a particular device of stored blood will perfuse the microvasculature of the patient receiving transfusion.
Human red blood cells (RBCs) are highly deformable 8 μm-in-diameter biconcave disks filled with a concentrated solution of hemoglobin and fine-tuned by evolution to perform their main task—the transport of oxygen and carbon dioxide. In order to accomplish that, RBCs need to pass through the intricate networks of microscopic blood vessels pervading every tissue and organ of the human body. When navigating through the microvascular networks (vessels ranging from 100 to 3 μm in diameter) at physiologically high hematocrits, RBCs must undergo a wide range of deformations. Such deformations include folding in small capillaries and shear deformations in large vessels of the microcirculation. The efficiency of oxygen delivery throughout the body is determined by the level of perfusion of the microvascular networks, which in turn depends on the microvascular fitness of RBCs.
A large number of experimental techniques aimed at quantifying the ability of RBC to deform under various conditions has been developed to date, including ektacytometry, micropipette aspiration, filtration through a polycarbonate or nickel mesh filter, single pore filtration, dragging by optical tweezers, and passage through parallel arrays of capillary-like microchannels.
Each of these methods allows for examination of the behavior of RBCs in response to a particular mode of deformation. While providing valuable information on the rheological properties of RBCs at the most basic level, these measurements are unable to predict how well a sample of RBCs will perfuse networks of microvessels at physiologically high hematorcits and the clinical significance of these measurements remains controversial.
Accordingly, there is a need for a system to help physicians assess the potential efficacy and toxicity of a stored RBCs sample blood prior to transfusion by measuring the ability of stored RBCs perfuse artificial, microfabricated microvascular networks that are structured to simulate human vasculature.